Background: S. aureus is the dominant infective trigger of atopic dermatitis (AD). How this bacterium drives type 2 allergic pathology in the absence of infection in AD patients is unclear.Objective: To identify the S. aureus-derived virulence factor(s) that initiates the cutaneous type 2-promoting immune response responsible for AD.Methods: In vitro human keratinocyte cell culture, ex vivo human skin organ explants and the eczema prone Nc/Tnd mouse were used as model systems to assess type-2 promoting immune responses to S. aureus. Identification of the bioactive factor was accomplished using Fast Protein Liquid Chromatography and mass spectrometry. Bioactivity was confirmed by cloning and expression in an E. coli vector system, and S. aureus Sbi mutant strains confirming loss of activity.Results: S. aureus was unique amongst staphylococcal species in its ability to induce the rapid release of constitutive IL-33 from human keratinocytes independent of the toll-like receptor pathway. Using the eczema-prone NC/Tnd mouse model, we showed that IL-33 was essential in inducing the immune response to S. aureus in vivo. By fractionation and candidate testing, we identified the Second Immunoglobulin-Binding Protein (Sbi) as the predominant staphylococcus-derived virulence factor that directly drives IL-33 release from human keratinocytes. Immunohistology of skin demonstrated that corneodesmosin, a component of corneodesmosomes that form key intercellular adhesive structures in the stratum corneum, was disrupted resulting in reduction of skin barrier function.Conclusion: S. aureus-derived Sbi is a unique type 2-promoting virulence factor capable of initiating the type-2 promoting cytokine activity underlying AD.
Background: Restoring apoptosis dysregulation via survivin inhibition has been investigated in several cancers. In Epstein-Barr Virus (EBV)-driven nasopharyngeal cancer (NPC), virally induced oncogenes can upregulate survivin. Therefore, we seek to investigate the therapeutic efficacy of YM-155 (a survivin inhibitor) in NPC, both in vitro and in vivo models. Methods: Cytotoxicity, apoptosis, and active-caspase 3 expression assays were performed.
Results: Both NPC tissue and cells expressed high levels of survivin which were inhibited by YM-155 in a dose-dependent manner. In addition, YM-155 induced apoptosis of NPC cells with an IC50 of 100 nM and inhibited tumor growth in vivo (P < 0.05). YM-155 in combination with cisplatin or radiation significantly increased overall cytotoxicity as compared to YM-155 monotherapy. In the xenograft model, YM-155 plus radiation additively achieved significantly higher percentage of active-caspase 3-positive tumor cells than radiation alone (P < 0.05). Conclusions: YM-155 is a potential therapeutic agent for NPC through inhibiting survivin and restoring apoptosis dysregulation. K E Y W O R D S apoptosis, nasopharyngeal carcinoma (NPC), radiotherapy, sepantronium bromide (YM-155), survivin (BIRC5)
In this study, TiO2 was successfully coated on Stober silica beads followed by depositing Au
nanoparticles on this core-shell structure. The size of the Au nanoparticles was well controlled in the
range of 2 – 7 nm. This composite exhibited high thermal stability. When used as a model catalyst for
oxidation of CO at low temperatures, the Au/TiO2/SiO2 showed a much higher catalytic activity than
the Au/SiO2 and Au/TiO2(P25) catalysts.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.